177Lu-PSMA-617 Improves Progression-Free Survival and Patient-Reported Outcomes Compared With Cabazitaxel for Men With Metastatic Castration-Resistant Prostate Cancer

The Phase 2 TheraP (ANZUP 1603) clinical trial demonstrated that a targeted radioligand therapy, lutetium-177 [¹⁷⁷Lu]-PSMA-617, was able to generate more prostate-specific antigen (PSA) responses of at least 50% reduction compared with the third-generation taxane cabazitaxel in men with metastatic castration-resistant prostate cancer (mCRPC) pretreated with docetaxel and a second-generation antiandrogen (enzalutamide or abiraterone) intravenous. ¹⁷⁷Lu-PSMA-617 is a radiolabeled small molecule that binds with high affinity to the enzymatic site of prostate-specific membrane antigen (PSMA), enabling highly targeted delivery of b-radiation to prostate cancer cells and disrupting the cells’ ability to replicate and/or triggering cell death.

In an updated analysis presented during the 2021 ASCO Genitourinary Cancers Symposium, Dr. Michael S Hofman (Peter MacCallum Cancer Centre, Melbourne, Australia) and colleagues reported that the patients receiving ¹⁷⁷Lu- PSMA-617 had improved progression-free survival (PFS), fewer grade 3-4 adverse events, and some improvements in patient-reported outcomes (PROs) compared to cabazitaxel.

TheraP demonstrated a 1-year PFS rate of 19% for ¹⁷⁷Lu-PSMA-617 compared to 3% for cabazitaxel (hazard ratio, 0.63; 95% confidence interval, 0.46-0.86; P=0.003). While many patients progressed, the results are a step forward for patients with mCRPC who have previously failed multiple other therapies. The lower rate of grade 3-4 adverse events (33% vs. 53%) and improvements in PROs related to fatigue, social functioning, insomnia, and diarrhea suggest that patients may better tolerate ¹⁷⁷Lu-PSMA-617 treatment. The findings support the evaluation of ¹⁷⁷Lu-PSMA-617 in larger, phase 3 trials and potential combination therapies.

Hiten D. Patel, MD, MPH, completed residency training in urologic surgery at the James Buchanan Brady Urological Institute and is currently a Clinical Instructor and Fellow in Urologic Oncology at Loyola University Medical Center. He has published studies related to epidemiology, comparative effectiveness, evidence-based reviews, and clinical trials in urologic oncology and related fields.

Bibliography:

Hofman MS, Emmett L, Sandhu SK, et al; ANZUP Cancer Trials Group. 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: Updated results including progression-free survival (PFS) and patient-reported outcomes (PROs) (TheraP ANZUP 1603). J Clin Oncol. 2021;39(6, suppl):3. Abstract 6. doi: 10.1200/JCO.2021.39.6_suppl.6

Hofman MS, Emmett L, Sandhu S, et al; TheraP Trial Investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021; 97(10276):797-804.. doi: 10.1016/S0140-6736(21)00237-3